Qinghua Wang Lab

Polycomb group (PcG) and trithorax group (TrxG) proteins are evolutionarily conserved regulatory factors that were initially discovered in Drosophila. PcG/TrxG proteins regulate chromatin structure and chromosome architecture through their interactions with polycomb/trithorax response elements (PRE/TREs), respectively. They are best known for their role in regulating homeotic genes during development in flies and vertebrates. However, it is now realized that PcG/TrxG proteins function as master transcriptional regulators for the expression of hundreds of other genes involved in differentiation, development, cell fate decisions and stem cell self renewal.

Despite these fundamental roles, very little is known about mammalian PRE/TREs, their recognizing proteins and their target genes. This knowledge gap has severely limited a complete mechanistic understanding of PcG/TrxG-caused gene regulation, including the mechanisms by which specific genomic loci are targeted, how the marks are “read” with respect to one another, and the means by which these marks are transmitted from one generation to the next. We are combining computational and experimental approaches to investigate PRE/TREs and their target genes in mammalian cells and the diseases resulting from the dysregulation of these processes. Such information will greatly deepen our understanding of the regulatory mechanisms by which embryonic stem cells and cancer cells differ from normal cells. Ultimately, the new insights gained are expected to aid in the development of therapeutic agents for clinical intervention.

Actin is one of the most abundant proteins in eukaryotic cells. It exists primarily as monomers (G-actin) bound by G-actin binding proteins that prevent spontaneous nucleation of new actin filaments, making nucleation the rate-limiting step in forming filamentous actin (F-actin). In response to cellular signals, specific actin nucleators initiate actin polymerization in a tight temporally and spatially controlled manner, which regulates many fundamental cellular processes including cardiac functions, cellular motility, cell shape and polarity determination, embryonic development and pathogen invasion. Understanding the de novo actin nucleation in response to stimuli lies in the core of modern biology. Our laboratory is combining bioinformatics, biochemistry and structural biology tools to investigate the molecular mechanisms of actin dynamics in muscle contraction and signal transduction.

Influenza virus is a negative-stranded RNA virus belonging to orthomyxoviridae family. Infections caused by influenza A and B viruses remain a major source of human morbidity and mortality worldwide, due to naturally evolving strains and to their potential use as man-made bio-weapons by terrorists. They both have a major surface glycoprotein HA that are responsible for binding to cell-surface receptors and for entering into host cells for replication. We are investigating the structures and functions of influenza A and B virus HAs. These include influenza A virus H1N1, H3N2, H5N1 and influenza B virus. Development of anti-influenza inhibitors is also underway.